Social determinants of fatty liver disease and its racial/ethnic disparities: The Multi-Ethnic Study of Atherosclerosis

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PROJECT SUMMARY Liver disease mortality is a key contributor to recent declines in life expectancy in the US. Decades of research have demonstrated the disproportionate burden of liver disease among racial/ethnic minorities and those with low-socioeconomic position. With the ongoing epidemic of obesity, and the increase in alcohol consumption, fatty liver diseases (FLD), including non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), have become the most prevalent chronic liver conditions affecting millions of people worldwide, constituting a major and growing public health problem. FLD epidemiology has largely focused on the role of individual-level behavioral factors, such as obesity and alcohol consumption, in FLD development. However, individual-focused therapeutic and preventive efforts have had limited success. For many chronic diseases, abundant literature has documented how social and physical environments pattern population health. In contrast, the empirical evidence of the role of social determinants of health with FLD and its disparities is extremely limited. Furthermore, the current paradigm to explain FLD disparities is heavily focused on genetic susceptibility (e.g. PNPLA3 gene variants). To address these research gaps, this project will test the novel hypothesis that individual and community- level social determinants influence FLD risk and their social and racial/ethnic disparities. To test this hypothesis, we propose to obtain and analyze longitudinal measures of liver fat and inflammation among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), the largest ongoing multi-racial population-based cohort study involving 6,814 men and women (22% Hispanic, 38% whites, 28% Blacks, 12% Chinese) from 6 geographically distinct areas of the US. MESA has the most comprehensive longitudinal data on socioeconomic (both individual and community level), psychosocial, neighborhood physical and social environment, environmental, behavioral, and biomedical (including genetics) factors and health outcomes with up to 21 years of follow up. Our specific aims are: 1) Characterize racial/ethnic disparities in FLD incidence, as measured by 10-year changes in CT- measured liver fat and liver enzymes, while accounting for genetic variants. 2) Examine the prospective association of individual-level socioeconomic position (SEP) and psychosocial stressors with FLD incidence and the contribution of SEP and psychosocial factors to socioeconomic and racial/ethnic disparities in FLD incidence. 3) Examine the prospective association of community-level social and physical features with FLD incidence and its racial/ethnic disparities in FLD incidence. 4) Examine the role of community-level social and physical features in magnifying individual-level genetic vulnerability by testing gene-by-environment interactions in the incidence of FLD between genetic variants and contextual factors. This project will constitute the largest, most rigorous and comprehensive investigation of the role of social determinants of health in the development and progression of FLD and its disparities.